HEAT-FLUX AND THE CALORIMETRIC-RESPIROMETRIC RATIO AS MEASURES OF CATABOLIC FLUX IN MAMMALIAN-CELLS

It is advocated that cellular heat flow rate (Phi = dQ/dt, where Q is heat) be expressed as an intensive quantity specific to cell size (X) and termed heat flux (J(Phi/X)). It has been the practice to cite such data on a 'per cell' basis, but it would be preferable to use biomass (cellular volume or mass). This quantity is shown to be a measure of metabolic activity and, more accurately, catabolic rate coupled to the demand for ATP in anabolic processes and work in the cell. Recent dev elopments in flow microcalorimetry and dielectric spectroscopy reveal that heat flux can be measured on-line, with the potential of industri al use as a control variable in the growth of hybridoma and geneticall y engineered cells. This is because the enthalpy change of growth can be regarded as a unique kind of stoichiometric coefficient directly re lated to the mass coefficients in the growth reaction. This can be ver ified by an enthalpy balance comparing data for material fluxes of cat abolites with the value for heat flux. Information revealed by the sto ichiometric growth equation can be used to improve medium design. The ratio of heat flux to oxygen consumption (flux) is known as the calori metric-respirometric (CR) ratio. It detects anaerobic processes when t he value is more negative than -450 (+/-5%) kJ mol(-1) O-2. These proc esses are found in cells growing under fully aerobic conditions, becau se glycolysis provides biosynthetic precursors with lactate as the by- product. It is suggested that the CR ratio would be a powerful on-line control variable for the growth of animal cells in bioreactors. (C) 1 997 Elsevier Science B.V.